# MG53 function in muscle aging

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $617,042

## Abstract

PROJECT SUMMARY
Elderly persons are susceptible to injury with compromised regenerative capacity of the skeletal muscle, leading
to gradual muscle weakness and loss of physical activity. Impaired myogenic satellite cell function is associated
with muscle aging. While it is known that exercise has many beneficial effects on aging and can improve satellite
cell function, searching for the putative myogenic factors that facilitate exercise-mediated improvement of muscle
function presents an attractive area for geriatric research. We know that exercise induces secretion of MG53
from skeletal muscle into circulation, which serves as a myokine to protect multiple tissues from injuries. However,
exercise-induced MG53 release is severely attenuated in aging. Chronic oxidative stress associated with aging
leads to MG53 aggregation that compromises MG53’s function in tissue repair and regeneration. We hypothesize
rejuvenating MG53’s myokine function will have benefits to aging. We have produced a transgenic mouse model
with sustained elevation of MG53 in the bloodstream, and found that these mice display remarkable muscle
regeneration following injury. We have data to show that treatment with recombinant human MG53 (rhMG53)
protein promotes proliferation and protects against stress-induced injury to muscle satellite cells. Therefore, we
propose to test if improvement of muscle satellite cell function by MG53 can provide long-term benefits to muscle
aging. Chronic oxidative stress and inflammation associated with aging may cause tissue injury and
consequently the elevation of MG53 in circulation. We will use a combination of live cell imaging, proteomic, and
CRISPR-gene editing tools to test if post-translational modification of MG53 in the serum can be a contributing
factor for MG53’s compromised tissue repair function during aging. Outcomes of the studies in this project can
lay the foundation and pave the way for our long-term goal of translating the basic findings of the benefits of
MG53 into therapeutic treatments of age-related muscle dysfunctions.

## Key facts

- **NIH application ID:** 10884459
- **Project number:** 5R01AG071676-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jianjie Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $617,042
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884459

## Citation

> US National Institutes of Health, RePORTER application 10884459, MG53 function in muscle aging (5R01AG071676-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884459. Licensed CC0.

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